Evolution of the immunosuppressive strategies for the intestinal and multivisceral recipients with special reference to allograft immunity and achievement of partial tolerance.
Introduction of new innovative immunosuppressive strategies has been the milestone of the recent evolution of intestinal and multivisceral transplantation. With new insights into the mechanisms of organ engraftment and acquired tolerance, the Pittsburgh tolerogenic protocol was recently introduced and consisted of two main therapeutic principles: recipient pretreatment with lymphoid ablating antibodies and minimal post-transplant immunosuppression with tacrolimus monotherapy. The reported herein improved survival and the striking ability to wean immunosuppression among the intestinal and multivisceral recipients pretreated with a single-dose of Thymoglobulin (rATG) or Campath-1H (alemtuzumab) supports our working hypothesis with successful induction of variable tolerance. It is important, however, that careful monitoring of subtle histologic changes in serial endoscopic-guided mucosal biopsies be carried out for early diagnosis of allograft immune activation with prompt restoration of the baseline immunosuppressive therapy. Future scientific discoveries with better understanding of the mechanisms of immune tolerance and clinical introduction of reliable assays will increase the chance and safety of achieving complete tolerance among the intestinal and other solid organ recipients. This review will focus on the historic evolution of the immunosuppressive and other management strategies utilized for the intestinal and multivisceral recipients at the University of Pittsburgh with special reference to allograft immunity and the successful achievement of partial tolerance.
Abu-Elmagd
Kareem M
KM
Intestinal Rehabilitation and Transplantation Center, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, PA, USA.
Costa
Guilherme
G
Bond
Geoffrey J
GJ
Wu
Tong
T
Murase
Noriko
N
Zeevi
Adriana
A
Simmons
Richard
R
Soltys
Kyle
K
Sindhi
Rakesh
R
Stein
William
W
Demetris
Anthony
A
Mazariegos
George
G
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000961:Antilymphocyte Serum; D065095:Calcineurin Inhibitors; D006084:Graft Rejection / Q000139:chemically induced; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007422:Intestines / Q000637:transplantation*; D009894:Opportunistic Infections / Q000517:prevention & control; D013375:Substance Withdrawal Syndrome; D016559:Tacrolimus / Q000009:adverse effects; D019172:Transplantation Conditioning; D023001:Transplantation Tolerance / Q000276:immunology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; C512542:thymoglobulin; D016559:Tacrolimus